The current standard of care in the US for women with advanced ovarian cancer is upfront surgical cytoreduction followed by systemic chemotherapy. There is extensive retrospective data to support aggressive surgery as important in improving overall survival. Some women, however, will present with disease that is not resectable (for example, intra-parenchymal liver metastases) or will be too medically ill to undergo surgery safely, without significant morbidity. In these cases, neoadjuvant chemotherapy has been shown to allow optimal cytoreduction without significant morbidity. However, not all women in either scenario (i.e., upfront surgery or neoadjuvant chemotherapy) will achieve first remission, and some will suffer disease progression during primary therapy. For women with platinum-resistant or refractory disease, extensive surgical efforts will not likely impact survival. Currently, it is not possible to identify these patients pre-operatively.
Presently, CA125, the only marker for ovarian cancer, is approved for use to assess treatment response. However, levels of CA125 are not predictive of successful cytoreduction. Moreover, some patients will experience recurrence without a rise in CA125, and recent data suggests that rising CA125 in the setting of recurrent disease is not useful in identifying the appropriate time to start treatment. Finally, it has been noted that the traditional disease response to treatment as measured by CT scan and CA125 may not apply to the newer biologic therapies. There is, therefore, a need to identify new markers to guide treatment decisions at different phases of this disease.
Vascular cell adhesion molecule-1 (VCAM-1) has been identified as a regulator of ovarian cancer peritoneal metastasis (Slack-Davis et al., 2009, Cancer Res.). Importantly, VCAM-1 is known to be expressed preferentially on the mesothelium of ovarian cancer patients compared to women with benign disease. Moreover, inhibition of VCAM-1 function decreases mesothelial invasion, diminishes tumor burden and increases survival in a mouse model of metastatic ovarian cancer.
Ovarian cancer is frequently diagnosed in advanced stage with extensive peritoneal metastasis and a 5-year survival of <25%. Platinum-resistance is a significant obstacle to successful treatment of ovarian cancer, and the inability to accurately monitor treatment response further confounds management of women with this disease.
There is a long felt need in the art for compositions and methods useful for diagnosing ovarian cancer, establishing treatment regimens for platinum-sensitive or platinum-resistant ovarian cancer, monitoring the progression of ovarian cancer, and monitoring the treatment response in ovarian cancer. The present application satisfies these needs.